Review
Chemistry, Medicinal
Hang Zhang, Haiwei Xu, Charles R. Ashby, Yehuda G. Assaraf, Zhe-Sheng Chen, Hong-Min Liu
Summary: This review highlights the recent achievements in drug design and mechanism studies of newly synthetic P-gp inhibitors in the past 5 years, which will help overcome multidrug resistance in cancer chemotherapy.
MEDICINAL RESEARCH REVIEWS
(2021)
Article
Cell Biology
Chung-Pu Wu, Megumi Murakami, Yu-Shan Wu, Ya-Chen Chi, Sung-Han Hsiao, Yang-Hui Huang, Tai-Ho Hung, Suresh Ambudkar
Summary: The study explored the potential of using branebrutinib to resensitize P-gp-overexpressing multidrug-resistant cancer cells to chemotherapy by inhibiting the drug transport function of P-gp. Results showed that branebrutinib could reverse P-gp-mediated MDR at sub-toxic concentrations while maintaining cytotoxicity against drug-sensitive parental cell lines and P-gp-overexpressing multidrug-resistant variants. This new pharmacological action of branebrutinib against P-gp activity warrants further investigation in future drug combination studies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Sachin Rathod, Heta Desai, Rahul Patil, Jayant Sarolia
Summary: This article discusses the significance of studying P-glycoprotein in drug delivery and highlights the effective reversal of P-gp inhibition using nonionic surfactants. Nonionic surfactants, being inert, non-toxic, and efficient, show potential as P-gp inhibitors and improve drug absorption and bioavailability through various mechanisms.
Article
Pharmacology & Pharmacy
Zhihao Liu, Xiaozhou Wen, Guangji Wang, Ying Zhou
Summary: 23-HBA significantly enhances the efficacy of anti-tumor agents in MDR cells, related to P-gp inhibition. Experimental results demonstrate that 23-HBA can improve cytotoxicity of ADR and VCR in MDR cells and affect the transport of P-gp substrates.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Kunal S. Taskar, Xinning Yang, Sibylle Neuhoff, Mitesh Patel, Kenta Yoshida, Mary F. Paine, Kim L. R. Brouwer, Xiaoyan Chu, Yuichi Sugiyama, Jack Cook, Joseph W. Polli, Imad Hanna, Yurong Lai, Maciej Zamek-Gliszczynski
Summary: This article discusses the role of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) in drug-drug interactions, drug absorption, and brain penetration. Based on clinical evidence, the article suggests that inhibition of P-gp or BCRP in the liver or kidneys has limited clinical implications on drug disposition.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Ashutosh Singh, Sandesh Kumar Patel, Prateek Kumar, Kanhu Charan Das, Deepanshu Verma, Rohit Sharma, Timir Tripathi, Rajanish Giri, Natalia Martins, Neha Garg
Summary: The resistance of cancer cells to chemotherapy is a major challenge in drug discovery. P-glycoprotein (P-gp) overexpression is directly linked to multidrug resistance (MDR) in cancer cells. Quercetin has been reported to inhibit the activity of P-gp, but the underlying mechanism is not fully understood. This study reveals the mechanistic understanding of quercetin-induced modulation of P-gp using molecular docking and molecular dynamics simulation.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Review
Pharmacology & Pharmacy
Sepideh Mirzaei, Mohammad Hossein Gholami, Farid Hashemi, Amirhossein Zabolian, Mahdi Vasheghani Farahani, Kiavash Hushmandi, Ali Zarrabi, Aaron Goldman, Milad Ashrafizadeh, Gorka Orive
Summary: In this review, the molecular pathways regulating P-gp and its involvement in DOX resistance are highlighted. The development of nanocarriers for co-delivery of DOX with anticancer compounds and genes is also discussed. Furthermore, the surface modification of nanocarriers to enhance selectivity towards cancer cells is explored.
DRUG DISCOVERY TODAY
(2022)
Article
Biochemistry & Molecular Biology
Yuedi Ding, Jun Fan, Zhenqiang Fan, Kai Zhang
Summary: The study demonstrated that ?-tocotrienol reversed the MDR of MCF-7/Adr cells by inhibiting the expression and function of mdr1/P-gp, as well as reducing the activation of the NF-?B signaling pathway.
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2021)
Article
Medicine, Research & Experimental
En Xu, Hao Zhu, Feng Wang, Ji Miao, Shangce Du, Chang Zheng, Xingzhou Wang, Zijian Li, Feng Xu, Xuefeng Xia, Wenxian Guan
Summary: This study investigated the potential of OSI-027 in inhibiting gastric cancer cells by arresting cell cycle and downregulating mTOR pathway and P-gp. The results showed that OSI-027 not only suppressed proliferation and enhanced apoptosis induced by oxaliplatin, but also exhibited synergistic cytotoxic effects with oxaliplatin in vitro. These findings suggest that dual mTOR1/2 inhibitors like OSI-027 may have potential as valuable treatments for gastric cancer.
CURRENT MOLECULAR MEDICINE
(2021)
Article
Oncology
Mingyue Liu, Chang Xu, Xiaochun Qin, Wenwu Liu, Deping Li, Hui Jia, Xudong Gao, Yuting Wu, Qiong Wu, Xiangbo Xu, Bo Xing, Xiaowen Jiang, Hongyuan Lu, Yingshi Zhang, Huaiwei Ding, Qingchun Zhao
Summary: This study investigated a novel P-gp inhibitor DHW-221 and its effects on non-small cell lung cancer (NSCLC) cells. DHW-221 exhibited antiproliferative activity, suppressed cell migration and invasion, and overcame resistance to paclitaxel by inhibiting P-gp. Furthermore, DHW-221 induced FOXO3a nuclear translocation via Akt inhibition, leading to mitochondrial apoptosis and G0/G1 cell cycle arrest.
FRONTIERS IN ONCOLOGY
(2022)
Article
Pharmacology & Pharmacy
Lei Zhang, Biwei Ye, Yunfeng Lin, Yi-Dong Li, Jing-Quan Wang, Zhuo Chen, Feng-Feng Ping, Zhe-Sheng Chen
Summary: In this study, the researchers investigated the effect of the CDK4/6 inhibitor, ribociclib, on multidrug resistance (MDR) mediated by P-glycoprotein (P-gp) in human epidermoid carcinoma cells. They found that ribociclib increased the efficacy of a P-gp substrate drug, colchicine, by down-regulating the expression of P-gp and increasing its ATPase activity. Docking studies suggested that ribociclib interacted with the drug-substrate binding site of P-gp. Additionally, ribociclib inhibited the drug efflux activity of P-gp, leading to increased intracellular accumulation of doxorubicin. These findings suggest that ribociclib may be a potential agent for combined therapy in cancers with P-gp-mediated MDR.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Libor Kostka, Ladislav Sivak, Vladimir Subr, Jirina Kovarova, Milada Sirova, Blanka Rihova, Radislav Sedlacek, Tomas Etrych, Marek Kovar
Summary: The derivative of protease inhibitor ritonavir (RD) was found to be a potent P-gp inhibitor and cancerostatic drug. In this study, high-molecular-weight HPMA copolymer conjugates with a PAMAM dendrimer core bearing both doxorubicin (Dox) and RD (Star-RD + Dox) were designed to increase the circulation half-life and maximize simultaneous delivery of Dox and RD into the tumor. It was found that Star-RD + Dox exhibited higher cytostatic and proapoptotic activities compared to other treatments in vitro, and also inhibited STAT3 signaling in vivo.
Article
Engineering, Environmental
Xiaqing Wu, Jiao Yan, Xiaoqing Han, Runxiao Zheng, Panpan Song, Yanjing Wang, Haiyuan Zhang
Summary: This study successfully reprogrammed tumor-associated macrophages (TAMs) from immunosuppressive to immunostimulatory state using Au-DP@FeCaC NPs, and achieved efficient chemotherapy of multidrug-resistant (MDR) cancer by releasing doxorubicin (Dox) under acidic conditions.
CHEMICAL ENGINEERING JOURNAL
(2022)
Article
Biotechnology & Applied Microbiology
Yanqing Wang, Gantao Chen, Fangfang Dai, Li Zhang, Mengqin Yuan, Dongyong Yang, Shiyi Liu, Yanxiang Cheng
Summary: This study investigated the impact of miR-21 on chemotherapy resistance in ovarian cancer cells, revealing that high expression of miR-21 can enhance proliferation, invasion, and migration abilities of OC cells. The interaction between CD44v6 and P-gp may play a role in mediating miR-21 involvement in chemotherapy resistance.
ONCOTARGETS AND THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Yunmoon Oh, Jin-Sol Lee, Ji Sun Lee, Jae Hyeon Park, Hyung Sik Kim, Sungpil Yoon
Summary: This study found that co-treatment with the JAK2 inhibitor fedratinib can enhance cytotoxicity in P-gp-overexpressing drug-resistant cancer cells when used in combination with the anticancer drug vinicristine. The cytotoxic effects are specific to resistant cancer cells and are mediated through cell cycle regulation and induction of apoptosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
